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Telltale Chemistry

For a woman with polycysticovary syndrome, life is full of unwelcome surprises. Starting at puberty, her body, surging with an unnatural burst of testosterone, will grow hair where it shouldn’t and produce acne and sweat. She may gain weight, often hurtling toward obesity despite her most fanatical efforts to shed pounds. She may become prone to diabetes and heart disease. But that’s not the worst of it. The cruelest blow is that all of this may happen without her knowing why. Though PCOS is the most common hormonal disorder among women of reproductive age, affecting as many as one in 10 women, it’s a tricky one for doctors to detect because its symptoms mimic many other ailments. Many women don’t discover they have PCOS until they try to get pregnant, their struggles to conceive only heightening their creeping doubt that something inside is wrong.

Short of a cure, what many women with PCOS hope for is a warning—a test that could alert future patients to the presence of the syndrome, giving them the head start they need to keep their symptoms in check. But no such test exists. PCOS involves multiple genes and an assortment of hormones that act on several different organs in the body. The best doctors can do now is diagnose PCOS by exclusion, ruling out other possible explanations in a process that can take months of testing.

But what if we knew what our bodies know? “Your body is very smart,” says Fariba Assadi-Porter PhD’94, an associate scientist in the CALS Department of Biochemistry. “It does really clever chemistry when it confronts disease. Before any physical signs show, your body is already adjusting its chemistry to defend itself.” Like sentinels prepared for combat, our body’s defenses react to conditions that we aren’t able to perceive. What we really need is news from the front—an alert that the enemies are massing at the gate.

Assadi-Porter is among a growing community of scientists who argue those alerts are all around us—in our blood, sweat, urine, tears and literally every breath we take. Those bodily fluids contain thousands of tiny molecules called metabolites, which are created when we digest foods, drugs or pollutants from the environment. By studying the profile of those metabolites, Assadi-Porter and other researchers hope to identify signals in the body’s internal chemistry that can help doctors diagnose hard-to-catch diseases like PCOS. Currently she is scouring blood, urine, sweat and breath samples from dozens of women with PCOS to look for metabolite profiles that are consistent with the syndrome. Once found, those telltale molecules could become the basis for a simple, noninvasive diagnostic test.

The project is a prime example of the promise of metabolomics, an exploding area of science that focuses on our chemical makeup at the most basic level. Smaller than cells, genes and proteins, metabolites are essentially the chopped-up products and by-products of our cells’ energy functions. Metabolic processes such as digestion create tiny fragments of foods and drugs, which float around as sugars or fatty acids inside us. Our bodies harbor at least 3,000 different types of metabolites, and their quantities are constantly changing, depending on factors such as diet, exercise and viral or bacterial infections.

Assadi-Porter says that shifting profile makes the metabolome—the term researchers use to describe the whole picture of our metabolites at any given moment—a compelling place to look for evidence of something new arising in our bodies. Her PCOS experiments—which won one of the first grants awarded by the university’s new research incubator, the Wisconsin Institutes of Discovery—are just the beginning. She predicts that within a decade a comprehensive screen of a patient’s metabolome will become a routine part of a trip to the doctor.

“This is very important for personalized medicine, to monitor peoples’ health status,” she says “With current technology we’re going to be able to do that. In the next ten years, we’re going to be there for sure.”

The idea behind metabolomics isn’t a new one. People have long understood that states of health and disease are somehow reflected in the concentrations of molecules inside our bodies. Physicians in ancient China used to set bowls of urine near colonies of ants to see if the insects swarmed. If they did, it meant the sample was full of sugar, confirming diabetes. Today doctors still look at sugar to diagnose the disease, measuring patients’ blood glucose levels. In the same way, they test cholesterol to monitor heart disease and urea and creatinine for kidney problems. Metabolomics is different mostly because of its scale: Instead of looking at the quantities of one or two isolated metabolites, it involves taking a broad view of scores or even hundreds of metabolites at once.